Cervical cancer is one of the leading causes of cancer death in women globally, despite the widespread use of cytology/human papillomavirus (HPV) screening. In the present study, we aimed to identify the potential role of microRNA (miRNA) as a diagnostic biomarker in the detection of cervical pre‐malignant lesions and cancer. In total, we recruited 582 patients with cervical diseases and 145 control individuals. The expression levels of six miRNAs (miR‐20a, miR‐92a, miR‐141, miR‐183*, miR‐210 and miR‐944) were found to be significantly up‐regulated in cervical cancer and pre‐malignant lesions compared to normal cervical samples, indicating that they are oncogenic miRNAs. Receiver operating characteristic curve analysis showed that these six miRNAs can be used to distinguish patients with cervical pre‐malignant lesions or cancer from normal individuals and they also had a good predictive performance, particularly in cervical lesions. Combined use of these six miRNAs further enhanced the diagnostic accuracy over any single miRNA marker, with an area under the curve of 0.998, 0.996 and 0.959, a diagnostic sensitivity of 97.9%, 97.2% and 91.4%, and a specificity of 98.6%, 96.6% and 87.6% for low‐grade lesions, high‐grade lesions and cancer, respectively. This six oncogenic miRNA signature may be suitable for use as diagnostic marker for cervical pre‐malignant lesions and cancer in the near future.

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We conducted a prospective randomized controlled trial with two screening rounds to evaluate the effectiveness of combining HPV testing with liquid‐based cytology (LBC) as a co‐test, compared to LBC only in cervical cancer screening of a Chinese population. First, 15,955 women aged 30–60 were randomized at a 1:1 ratio into an intervention group (Digene Hybrid Capture 2 HPV test with LBC) and a control group (LBC alone). Women in the intervention group would be referred for colposcopy and biopsy immediately if they were found to have high‐risk HPV regardless of cytology results. The detection of cervical intraepithelial neoplasia grade 2 or above (CIN2+) lesions was significantly higher in the intervention group compared to the control (0.95% vs. 0.38%, OR 2.50, 95% CI 1.65–3.88). At the subsequent round of screening approximately 36 months later, CIN2+ detection was significantly lower in the intervention group (0.08% vs. 0.35%, OR 0.23, 95% CI 0.08–0.57). Over the two rounds of screening, the total detection of CIN2+ was higher in the intervention group (1.01% vs. 0.66%, OR 1.53, 95% CI 1.09–2.19). There was a fourfold increase (10.6% vs. 2.4%, p < 0.001) in the number of colposcopies performed in the intervention arm. Adding a high‐risk HPV test to cytology for primary cervical screening led to earlier detection of clinically significant preinvasive lesions, resulting in a reduced detection of CIN2+ lesions in subsequent rounds and an increased rate of colposcopy.

Background and Objectives:Ischemic stroke despite direct oral anticoagulant (DOAC) is increasingly common and portends high risk of subsequent ischemic stroke. Efficacy and safety of antithrombotic regimens following the condition are unclear. We aimed to compare the outcomes of patients with ischemic stroke despite DOAC with and without an alternative antithrombotic regimen, and determine the risk factors of recurrent ischemic stroke while on anticoagulation.Methods:In a population-based, propensity-score weighted, retrospective cohort study, we compared the clinical outcomes of DOAC-to-warfarin switch, DOAC-to-DOAC switch (DOACswitch) or addition of antiplatelet agents, with unchanged DOAC regimen (DOACsame) among non-valvular atrial fibrillation (NVAF) patients who developed the first ischemic stroke despite DOAC from 1stJanuary 2015 to 31stDecember 2020 in Hong Kong. Primary outcome was recurrent ischemic stroke. Secondary outcomes were intracranial hemorrhage, acute coronary syndrome and death. We performed competing risk regression analyses to compare the clinical endpoints, and determined the predictors of recurrent ischemic stroke in an unweighted multivariable logistic regression model.Results:During the 6-year study period, among 45,946 AF patients on DOAC as stroke prophylaxis, 2,908 patients developed ischemic stroke despite DOAC. 2,337 NVAF patients were included in the final analyses. Compared to DOACsame, warfarin (aHR 1.96, 95%CI 1.27-3.02, p=0.002) and DOACswitch(aHR 1.62, 95%CI 1.25-2.11, p-value <0.001) were associated with increased risk of recurrent ischemic stroke. In DOACsamegroup, adjunctive antiplatelet agent was not associated with reduced risk of recurrent ischemic stroke. Diabetes mellitus, concurrent cytochrome P450/P-glycoprotein (CYP/P-gp) modulators and large artery atherosclerotic disease (LAD) were predictors of recurrent ischemic stroke.Discussion:In NVAF patients with ischemic stroke despite DOAC, the increased risk of recurrent ischemic stroke with switching to warfarin called for caution against such practice, while the increased ischemic stroke with DOAC-to-DOAC switch demands further studies. Adjunctive antiplatelet agent did not appear to reduce ischemic stroke relapse. As diabetes mellitus, use of CYP/P-gp modulators and LAD were predictors of recurrent ischemic stroke, further investigations should evaluate if strict glycemic control, DOAC level monitoring and routine screening for carotid and intracranial atherosclerosis may reduce ischemic stroke recurrence in these patients.Classification of Evidence:This study provides Class II evidence that in patients with non-valvular atrial fibrillation suffering an ischemic stroke while being treated with a DOAC, continuing treatment with that DOAC is more effective at preventing recurrent ischemic stroke than switching to a different DOAC or to warfarin.